Biological Therapeutics for Infection-Relating Disorders or Conditions

ABSTRACT

The present invention discloses products and the methods of uses of the products for preventing and treating infectious diseases and the disorders or conditions inducible by harmful antibodies. The harmful antibodies are induced during infection, or vaccination, or use of therapeutic antibodies. The products of the present disclosure comprise immunoglobulin products, serum or plasma, specific antibodies to viral pathogens.

CLAIM OF PRIORITY

This application claims priority to U.S. Provisional Patent ApplicationSer. No. 61/792,888, filed Mar. 15, 2013, entitled “Biologicaltherapeutics for infection-relating disorders or conditions”, the entirespecification and disclosure of which is herein incorporated byreference.

FIELD OF INVENTION

The present disclosure relates generally to the fields of medicine andepidemiology, and in particular, to one or more products and methods fortreating or preventing infections caused by viral pathogens, diseasesand. conditions caused by harmful antibodies which are inducible byinfectious pathogens, vaccines and therapeutic antibodies.

BACKGROUND OF THE INVENTION

An infectious disease is a clinically evident disease of humans oranimals. Information collected by the World Health Organization (WHO) onglobal deaths shows that worldwide mortality due to infectious diseasesis as high as 25.9% of all deaths, or 14.7 million deaths in 2002 (WHOWorld Health Report 2002). The current numbers are even higher.

Influenza infections especially an influenza pandemic threats people'shealth and economy globally. There is a big concern on a possibleinfluenza pandemic causing by highly pathogenic H5N1 (avian or bird)influenza vims which will cause much more deaths than the 2009 swineinfluenza pandemic (WHO). Currently, there are no effective medicinesfor the treatment of a serious condition of an influenza infectionespecially a serious condition after 48 hours of an influenza infection.

Vaccines are the most effective approach to prevent infectious diseases.However, vaccines are not perfect as they may cause serious adversereactions even death. For example, the swine influenza vaccine in 1976might be related to about 500 cases of Guillain-Barre syndrome (GBS) and25 deaths that the vaccine had to be called off (US CDC, VAERS). The2009 monovalent H

1 (swine) influenza vaccine might have induced 636 serious healthevents, including 103 cases of GBS and 51 deaths in the United States(US CDC, VAERS). Thus far, there is no direct proof between influenzavaccines and the serious side effects. Neither, there are not anymedicines for preventing and treating the serious adverse reactions ofinfluenza vaccines or other vaccines due to the unclear pathogenicmechanisms.

Every year an estimated 2.64 million babies die at 28 weeks' gestationor more (still birth) (Tlenadv. V., et al. Major risk factors forstillbirth in high-income countries: a systematic review andmeta-analysis. Lancet, Apr. 16, 2011; 377:1331-1340), and 4 millionbabies die in the first 4 weeks of life (the neonatal death)(Lawn J E,Cousens S, Zupan J. 4 million Neonatal deaths: When? Where? Why? Lancet,2005 Mar. 5-1 1; 365(9462):891-900). One potential risk factor may berelated to infections. Nevertheless, how an infection induces fetal orneonatal deaths is unclear.

We have developed viral free animal models by injecting variousanti-pathogen antibodies into chicken embryos or pregnant mice. Theresults of the experiments with those animal models indicated that someof anti-pathogen antibodies induced during an infection (e.g. aninfluenza infection) or by a vaccine (e.g. an influenza vaccine) can beharmful and cause serious conditions such as GBS even death. Therapeuticproducts for preventing and treating the disorders caused by such toxicantibodies were tested using the animal models.

SUMMARY OF THE INVENTION

The present invention discloses products and the methods of uses of theproducts for preventing and treating infectious diseases and thedisorders or conditions inducible by harmful antibodies. The harmfulantibodies are induced during infection, or vaccination, or use oftherapeutic antibodies. The products of the present disclosure compriseimmunoglobulin products, serum or plasma, specific antibodies to viralpathogens.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT(S)

While the present disclosure is susceptible of embodiment in manydifferent forms, there will be described herein in detail, preferred andalternate embodiments of the present disclosure. It should be understoodhowever, that the present disclosure is to be considered anexemplification of the principles of the invention and is not intendedto limit the spirit and scope of the invention and/or claims of theembodiments illustrated.

Dualistic Roles of Antibodies

Based on the traditional concept, the antibodies induced by aninfectious pathogen or by a vaccine are protective to a host becausethey can neutralize the pathogen and prevent or treat the infectiousdisease. However, the roles of such antibodies can be dualistic. Some ofthe antibodies can cross react to certain cells, tissues or organs of ahost, triggers certain harmful reactions such as antibody-dependentcytotoxicity or defects in signal transduction pathways, and causedamages or disorders of the tissues and organs. For example, anti-viralantibodies can bind to host tissues and organs, irratate and causedisorders of the tissues and organs (e.g. autoimmune diseases asdescribed in PCT/US2007/018258 and PCT/US2009/039810).

It is known that in an acute viral infection or a vaccination,antibodies against a pathogen (e.g. a virus) or a vaccine are inducedand elevated one week after infection or vaccination and reach peaklevels at two weeks after the infection or the vaccination. Some of suchantibodies can bind to certain types of host cells or tissues or organs.This process can be pathogenic and cause severe diseases or conditionseven death. For example, anti-rotavirus antibodies bind to theproliferating goblet cells during a rotavirus infection(PCT/US2009/039810 and US201 10085981). Injection of high dose of theanti-rotavirus antibodies to pregnant mice induced deaths and bile ductepithelium proliferation (inflammation) of mouse pups born to the dames(PCT/US2009/039810, US201 10085981). Further, administration of highdose of the anti-rotavirus antibodies to mouse pups before or afterrotavirus infection caused deaths or severer infection of mouse pups asdescribed in PCT/US2009/039810 and US201 10085981.

In the present disclosure, the term “harmful antibodies” refers to anyantibodies capable of causing pathogenic reactions and damages ordisorders of the cells, tissues and organs of a host. The harmfulantibodies can be induced during an infection (e.g. an influenzainfection) or a vaccination (e.g. an influenza vaccination), orpassively introduced (e.g. a therapeutic antibody). The diseases orconditions caused by harmful antibodies of the present disclosureinclude but not limited to infectious diseases, serious adversereactions of vaccines or therapeutic antibodies, infection-relatingautoimmune diseases, allergies, and inflammation, infection-relatingtumors, and any other disorders (known or unknown) inducible by harmfulantibodies.

Animal Models for Pathogenic Study and Evaluating the Safety of Vaccinesand Antibodies

One embodiment of the present invention discloses the experimentalmodels by injecting anti-pathogen antibodies into chicken embryos orpregnant mice or newborn mouse pups.

One aspect of the present invention is to disclose the experimentalmodel which is developed by injecting human anti-influenza immune seraor other anti-pathogen antibodies into chicken embryos and observing thehealthy status of the newborn chicks as described in exemplification.The human immune sera were from patients either with natural influenzainfection or with influenza vaccination, or human immune sera from otherinfectious diseases. As described in exemplification, injection of thehuman anti-influenza viral sera into chicken embryo at day 16 (E16) andE19 induced the leg disability of newborn chicks which is similar to theGuillain-Barre syndrome (GBS) in humans. The frequencies of GBS-likeconditions induced by the anti-influenza viral antibodies are listed inTable 1. The results with this animal model indicated that theantibodies induced by the 2009H1M (swine) virus is at the highest riskfor inducing GBS (42.5%). followed by the antibodies induced by the Binfluenza virus (32.5%), the avian H5N1 virus (27.5%), the seasonal HIMvirus (17.5%) and the H3N2 virus (15.0%). Further, injection of humananti-influenza viral sera induced fetal and neonatal deaths. The deathrates are listed in Table 2. The results with this animal modelindicated that the antibodies induced by the B influenza virus is at thehighest risk for inducing fetal and neonatal deaths (65.0%), followed bythe antibodies induced by the avian H5N1 virus (57.5%), 2009H1N1 (swine)virus (52.5%), the H3N2 virus (37.5%) and the seasonal H1N1 virus(15.0%). As a control, the anti-respiratory syncytial viruses (RSV)serum did not cause significant GBS-like condition nor deaths (Tables1-2).

The experimental models can be used but not limited for the pathogenicstudy of infectious diseases, autoimmune diseases such as Guillain-Barresyndrome (GBS) or GBS-like condition, infection-relating fetal andneonatal deaths, adverse reactions of influenza vaccines and othervaccines or therapeutic antibodies; for screening drugs for preventionand treatment of the disorders or conditions caused by harmfulantibodies (e.g. those as mentioned above); or for the rapid evaluationof the safety of vaccines (e.g. influenza vaccines) and therapeuticantibodies. Other embodiments besides the above may be articulated aswell. Numerous other objects, features and advantages of the presentdisclosure will become readily apparent from the detailed description.

Another aspect of the present invention is to disclose anotherexperimental model which is developed by injecting anti-influenza immunesera or other anti-pathogen antibodies to pregnant mice and observingthe healthy status of the pregnant dames and newborn mouse pups asdescribed in exemplification. As described in exemplification, injectionof the human anti-influenza viral sera into pregnant mice at pregnantday 16 (E16) and E19 induced abortion of the pregnant mice, immature ordelayed delivery, and fatal and neonatal death of the newborn mouse pupsdelivered to the dames. The frequencies of fatal and neonatal death ofthe newborn mouse pups are listed in Table 3. The results with thisanimal model indicated that the antibodies induced by the H5N1 (avian)virus is at the highest risk for inducing death (34.6%), followed by theantibodies induced by the seasonal H 1N 1 virus (26.7%), and the H3N2virus (26.5%), B influenza virus (23.5%), and the 2009H1N1 (swine) virus(22.9%). The frequencies of abortion of the pregnant mice are listed inTable 4. The results with this animal model indicated that theantibodies induced by the B influenza virus is at the highest risk forinducing abortion (33.3%), followed by the antibodies induced by the2009H1N1 (swine) virus (31.3%), the H3N2 virus (28.6%), the seasonalH1N1 virus (21.4%), and the H5N1 (avian) virus (20.0%). The histologychanges of the dead mice showed that the infiltration with red bloodcells, inflammatory cells and proliferation of epithelium cells, andlocal tissue lesions were observed in the tissues of lung, brain, heartand fiver of the dead chicks and mouse pups. In addition, binding ofhuman IgG to those organs was detectable with the tissue sections of thedead chicks and mouse pups.

Taken together, the data with the animal models mentioned above stronglyindicated that influenza infections or influenza vaccinations ofpregnant females may be harmful to the fetus and newborns because someof the antibodies inducible by influenza vaccines may induce abortion,immature or delayed delivery and fetal and neonatal deaths. Further,some antibodies inducible by influenza viruses or influenza vaccines maycause autoimmune diseases or serious adverse reactions such as GBS orGBS-like condition and deaths. Similarly, some antibodies inducible byother pathogens or other vaccines may also cause autoimmune diseases orserious adverse reactions.

The experimental models can be used but not limited for the pathogenicstudy of infectious diseases, autoimmune diseases, infection-relatingfetal and neonatal deaths, adverse reactions of influenza vaccines andother vaccines or therapeutic antibodies; for screening drugs forprevention and treatment of the disorders or conditions caused byharmful antibodies (e.g. those as mentioned above}; or for the rapidevaluation of the safety of vaccines (e.g. influenza vaccines) andtherapeutic antibodies. Other embodiments besides the above may bearticulated as well. Numerous other objects, features and advantages ofthe present disclosure will become readily apparent from the detaileddescription of the experimental models.

New Pathogenic Mechanisms of Infections and Infection-Relating Disordersor Conditions

One embodiment of the present invention discloses the new pathogenicmechanisms of infection-relation disorders or conditions including butnot limited to infectious diseases, autoimmune diseases, cancer andother disorders possibly relating to infections.

One aspect of the present invention is to disclose a new concept of thepathogenic mechanisms of an infection. The mechanisms include but notlimited to: 1) The initial, primary damage of cells, tissues or organscaused by viruses within week one; 2) The secondary damage is caused byanti-viral antibodies which are elevated from week one and reach peaklevels from week two to week three after viral clearance; 3) thesecondary damage can add further damage to the primary damage and causesever disorders even death (primary plus secondary damages). 4} Thesecondary damage can be longer and broader because antibodies persistmuch longer than viruses. The primary plus secondary damages asmentioned above can cause serious conditions during an acute infection:and the persist antibodies can cause or make worse of the disorders orconditions such as autoimmune diseases, allergies, cancers and otherdisorders possibly relating to toxic antibodies.

Based on the pathogenic mechanisms mentioned above, antibodies againstthe viral strains of the 1918 and the 2009 influenza pandemic can be themajor death cause of those influenza pandemics. This is supported byfollowing evidences: 1) about ⅔ of deaths caused by the influenzainfections occurred between week 2 to week 3 (Edwin O. Jordan. EpidemicInfluenza—A survey, 1927) which was consistent to the time period of theantibody pick levels; and 2) the majority of severe or lethal infectionshappened to the youth (Edwin O. Jordan. Epidemic Influenza—A survey,1927; WHO: Pandemic (HIM) 2009-update 41) because younger people couldinduce higher levels of antibodies.

Another aspect of the present invention is to disclose a new pathogenicmechanism and the cause of autoimmune diseases. Based on the aboveobservations, some of the antibodies inducible by a pathogen or by avaccine can bind to self cells or tissues or organs and mislead theimmune response to attack the self. One example is that antibodiesinducible by influenza viruses or influenza vaccines could cause GBS orfetal and neonatal deaths as described above. Another example is thatinjection of high dose of the anti-rotavirus antibodies to pregnant miceinduced deaths and bile duct obstruction (biliary atresia) due toepithelium proliferation (inflammation) of mouse pups born to the dames(PCT/US2009/039810, US201 10085981).

Another aspect of the present invention is to disclose a new pathogenicmechanism of cancers or other disorders (known or unknown). Many otherdisease processes such as cancers, diabetes, heart disease, and otherdisorders (known or unknown) arise from uncontrolled cell growth ordefects in signal transduction pathways. Some of the antibodies inducedduring an infection or a vaccination or a therapeutic antibody can bindto certain cell-surface molecules and induce cellular proliferation ordefects in signal transduction pathways. Repeatedly or persistentstimulation with such harmful antibodies can lead to uncontrolledcellular proliferation or defects in signal transduction pathways thatlead to the development and progression of many types of cancers,autoimmune diseases, or other disorders (known or unknown). For example,anti-HIV antibodies stimulated proliferations of human lung cancer cells(A549) and liver cancer cells (HepG-2). Leukemia or lymphomas can becaused by some harmful antibodies inducible during an acute or a chronicinfection (e.g. a human T-cell leukemia virus infection). The harmfulantibodies can bind to the white blood cells including lymphocytes andstimulate the uncontrolled cellular proliferation of those blood cells,leading to leukemia or lymphomas.

Other embodiments besides the above may be articulated as well. Numerousother objects, features and advantages of the present disclosure willbecome readily apparent from the new disease causes (harmful antibodies)and the new pathogenic mechanisms.

Diseases and Conditions Inducible by Harmful Antibodies

In the present disclosure, the harmful antibodies can be induced duringan infection (e.g. an influenza infection) or a vaccination (e.g. aninfluenza vaccination), or passively introduced (e.g. a therapeuticantibody). The diseases or conditions caused by harmful antibodies ofthe present disclosure include but not limited to infectious diseases,serious adverse reactions of vaccines or therapeutic antibodies,infection-relating autoimmune diseases, allergies, and inflammation, andinfection-relaxing tumors, and other disorders (known or unknown).

The term “infectious diseases” refers to the invasion of a hostorganism's bodily tissues by disease-causing organisms, theirmultiplication, and the reaction of host tissues to these organisms andthe toxins they produce. A short-term infection is an acute infection. Along-term infection is a chronic infection. Pathogens specific toinfectious diseases suitable for use in this process include, but arenot limited to viruses, bacteria, parasites, fungi, viroids, prions,protozoa, and insects, etc. Types of pathogens include but not limitedto any types of pathogens, live or dead or inactivated, fresh or dried,fixed or frozen, whole or part or fragment, sections, smears,homogenates, lysates, and extracts of pathogens, and etc., withoutlimitation. Examples of infections include but not limited to thedisorders caused by influenza viruses, reoviruses, rotaviruses,cytomegaloviruses (CMV), Epstein-Barr viruses (EBV), adenoviruses,hepatitis viruses including HAV, HBV, HCV, human immunodeficiency virus(HIV), human T-cell leukemia viruses (HTLV), human papilloma viruses(HPV), polio viruses, parainfluenza viruses, measles viruses, mumpsviruses, respiratory syncytial viruses (RSV), human herpes viruses(HHV), herpes simplex vims (HSV), Varicella-Zoster Virus, choleraviruses, pox virus, rabies virus, distemper virus, foot and mouthdisease viruses, rhinoviruses, Newcastle disease viruses, pseudorabiesvirus, cholera, syphilis, anthrax, leprosy and bubonic plague,rickettsias, neisseria gonorrhoeae, bordetella pertussis, escherichiacoli, salmonella enterica, vibrio cholerae, pseudomonas aeruginosa,yersinia pestis, franciseila tularensis, Haemophilus influenzae, purplesulfur bacteria, Helicobacter pylori, Campylobacter jejuni, bacillusanthracis/cereus/thuringiensis, Clostridium tetani, Clostridiumbotulinum, staphylococci, streptococci, pneumococci, streptococcuspneumoniae, mycoplasmas, bacteroides fragilis, mycobacteriumtuberculosis, mycobacterium leprae, corynebacterium diphtheriae,treponema pallidum, borrelia burgdorferi, chlamydia trachomatis,chlamydia psittaci, phycocyanin, phycoerythrin, mitochondria,chloroplasts, etc without limitation.

According to the present invention, the term “infection-relatingautoimmune diseases, allergies and inflammation” refers to the disordersor conditions caused by harmful antibodies induced during an infectionor a vaccination or an antibody therapy. The disorders or conditionsusually arise after a period time (e.g. within 4-8 weeks) of aninfection or a vaccination. Examples of infection-relating autoimmunediseases, allergies and inflammation include but not limited toGuillain-Barre syndrome, autism, Kawasaki's disease, biliary atresia,primary biliary cirrhosis, systemic lupus erythematous, leukemia, acuteleukemia, rheumatoid arthritis, adult onset diabetes mellitus (Type IIdiabetes), Sjogren's syndrome, juvenile onset diabetes mellitus,Hodgkin's and non-Hodgkin's lymphoma, malignant melanoma,cryoglobulinemia, hepatitis B virus infection, hepatitis C virusinfection, Wegener's granulomatosis, inflammatory bowel disease,polymyositis, dermatomyositis, multiple endocrine failure, Schmidt'ssyndrome, autoimmune uveitis, Addison's disease, adrenaiitis, Graves'disease, thyroiditis, Hashimoto's thyroiditis, autoimmune thyroiddisease, pernicious anemia, gastric atrophy, chronic hepatitis, lupoidhepatitis, atherosclerosis. presenile dementia, demyelating diseases,multiple sclerosis, subacute cutaneous lupus erythematosus,hypoparathyroidism, Dressler's syndrome, myasthenia gravis, autoimmunethrombocytopenia, idiopathic thrombocytopenic purpura, hemolytic anemia,autoimmune hemolytic anemia, dermatitis herpetiformis, alopecia areata,autoimmune cystitis, pemphigoid, scleroderma, progressive systemicsclerosis, CREST syndrome (calcinosis, Raynaud's esophageal dysmotility,sclerodactyly, and telangiectasia), male or female autoimmuneinfertility, ankylosing spondylitis, ulcerative colitis, Crohn'sdisease, mixed connective tissue disease, polyarteritis nodosa, systemicnecrotizing vasculitis, juvenile onset rheumatoid arthritis,glomerulonephritis, atopic dermatitis, atopic rhinitis, Goodpasture'ssyndrome, Chagas' disease, sarcoidosis, rheumatic fever, asthma,recurrent abortion, anti-phospholipid syndrome, farmer's lung, erythemamultiforme, pemphigus vulgaris, pemphigus, bullous pemphigoid,postcardotomy syndrome, Cushing's syndrome, autoimmune chronic activehepatitis, bird-fancier's lung, asthma, allergic disease, allergicencephalomyelitis, toxic necrodermal lysis, alopecia, Alport's syndrome,alveolitis, allergic alveolitis, fibrosing alveolitis, interstitial lungdisease, erythema nodosum, pyoderma gangrenosum, transfusion reaction,leprosy, malaria, leishmaniasis, trypanosomiasis, chronic fatiguesyndrome, fibromyalgia, Takayasu's arteritis, polymyalgia rheumatica,temporal arteritis, schistosomiasis, giant ceil arteritis, ascariasis,aspergillosis, Sampter's syndrome (triaditis also called, nasal polyps,eosinophilia, and asthma), Behcet's disease, Caplan's syndrome, dengue,encephalomyositis, endocarditis, myocarditis, endomyocardial fibrosis,endophthalmitis, erythema elevatum et diutinum, psoriasis,erythroblastosis fetalis, fascitis with eosinophilia, Shulman'ssyndrome. Felty's syndrome, filariasis, cyclitis, chronic cyclitis,heterochromia cyclitis, Fuch's cyclitis, IgA nephropathy,Henoch-Schonlein purpura, glomerulonephritis, graft versus host disease,transplantation rejection, cardiomyopathy, Alzheimer's disease,parvovirus infection, rubella virus infection, post vaccinationsyndromes, congenital rubella infection, renal cell carcinoma, multiplemyeloma, Eaton-Lambert syndrome, relapsing polychondritis, Waldenstrom'smacroglobulinemia, mumps virus infection, thrombotic throbocytopenicpurpura, and any other disorder or conditions in which the specificrecognition of the host by pathogen-inducible or vaccine-inducibleantibodies is suspected or shown to be important in any aspect of thepathogenesis of the clinical illness. According to the presentinvention, the term “serious adverse reactions of vaccines ortherapeutic antibodies” refers to the severe disorders or conditionscaused by harmful antibodies induced during a vaccination or an antibodytherapy. The disorders or conditions usually arise after a period time(e.g. within 4-8 weeks) of a vaccination or an antibody therapy.Examples of serious adverse reactions of vaccines of the presentdisclosure include but not limited to deaths, acute infant deathsyndrome, Guillain-Barre syndrome, Kawasaki's disease, acute leukemia,allergies, serious allergic reactions, asthma, epilepsy, immune systemdisorders, behavior disorders, nervous system injur}, permanent braindamage, learning difficulties, seizure, severe seizures, loweredconsciousness, autism, long-term coma, headaches, upper or lowrespiratory tract infection, joint pain, abdominal pain, cough, nausea,diarrhea, high fever, blood in the urine or stool, pneumonia,inflammation of the stomach or intestines, non-stop crying, fainting,deafness, temporary low platelet count, hives, pain in the joints,intussusception, vomiting, severe nervous system reaction,life-threatening severe illness with organ failure, still birth,neonatal deaths, and any other disorder or conditions in which thespecific recognition of the host by vaccine-inducible antibodies issuspected or shown to be important in any aspect of the pathogenesis ofthe clinical illness.

According to the present invention, the term “infection-relating tumors”refers to the disorders or conditions with uncontrolled cell growthcaused by harmful antibodies induced during an acute infection, or avaccination or an antibody therapy, or a chronic infection, Thedisorders or conditions usually arise after a period time of an acuteinfection or a vaccination or an antibody therapy (e.g. acute leukemia).In addition, many tumors are developed by repeated stimulation ofantibodies induced during a chronic infection. Examples ofinfection-relating tumors or cancers of the present disclosure includebut not limited to acute or chronic leukemia, Hodgkin's andnon-Hodgkin's lymphoma, malignant melanoma, tumors or cancers developedduring infections of HIV, HTLV, HBV, HCV, EBV, CMV, HPV, HHV, HSV,adenoviruses, measles viruses, mumps viruses, varicella-zoster virus,lung cancers, liver cancer, prostate cancer, breast cancer, coloncancers, gastrointestinal cancers, pancreas cancers, cervical cancers,overall cancers, thyroid cancers, neurological cancers or tumors, renalcell carcinoma, kidney cancers, multiple myeloma, hemangioma, heartfibroid, and any other disorder or conditions in which the specificrecognition of the host by pathogen-inducible or vaccine-inducibleantibodies is suspected or shown to be important in any aspect of thepathogenesis of the clinical illness.

Therapeutic Products for Disorders or Conditions Inducible by HarmfulAntibodies

Based on the new causes and the new pathogenic mechanisms of thedisorders or conditions inducible by harmful antibodies as mentionedabove, one embodiment of the present invention discloses substances orproducts (new or existing) and approaches and the methods of uses of thesubstances or products (new or existing) and approaches for preventingand treating the disorders or conditions inducible by harmful antibodiesby interrupting the binding of the harmful antibodies to host cells,tissues and organs, or by neutralizing the harmful antibodies. Theproducts of the present disclosure include but not limited to serum orplasma, immunoglobulin, non-harmful antibodies, pathogen-derivingproducts, host-deriving products, saccharides, and any other substancesor products (new or existing) capable of competing or neutralizingharmful antibodies.

Immunoglobulin or Serum or Plasma for Disorders Caused by HarmfulAntibodies

One embodiment of the present invention discloses immunoglobulinproducts or serum or plasma and the methods of using the immunoglobulinproducts or the serum or the plasma for preventing and treating diseasesand conditions relating to harmful antibodies from an infection or avaccination, or an antibody therapy. The immunoglobulin orimmunoglobulin in serum or plasma can compete, dilute and interrupt thebinding of harmful antibodies to host cells, or tissues or organs, andprotect the damages from harmful antibodies.

One aspect of the present invention discloses immunoglobulin products orserum or plasma for preventing and treating diseases or conditions (e.g.fetal and neonatal death) caused by harmful antibodies.

Wherein, the amounts or concentrations of an immunoglobulin product arefrom about 0.001 gram (g) to about 100 g. The amounts of a serum orplasma are from about 0.1 ml to 1000 ml.

Wherein the immunoglobulin product or the serum or the plasma are in aform of a solution, a lyophilized, an injectable, an infusion, or a formconjugated to a nano-particle, or other using forms well known to thoseof ordinary skill in the relevant arts.

Wherein, the immunoglobulin products or the serum or the plasma are usedfor preventing or treating the diseases or conditions caused by harmfulantibodies of the present disclosure. The diseases or conditions includebut not limited to infectious diseases, serious adverse reactions ofvaccines or therapeutic antibodies, infection-relating autoimmunediseases, allergies, and inflammation, and infection-relating tumors,and other disorders (known or unknown) as mentioned above.

Another embodiment of the present invention discloses the methods ofusing immunoglobulin products or serum or plasma for preventing andtreating the diseases or conditions caused by harmful antibodies of thepresent disclosure. The diseases or conditions include but not limitedto infectious diseases, serious adverse reactions of vaccines ortherapeutic antibodies, infection-relating autoimmune diseases,allergies, and inflammation, and infection-relating tumors, and otherdisorders (known or unknown) as mentioned above.

One aspect of the methods is consisted administrate immunoglobulinproducts or serum or plasma to a human or an animal individual at riskof suffering or developing harmful antibody-inducible diseases orconditions as mentioned above.

Another aspect of the methods is consisted of administrateimmunoglobulin products or serum or plasma to the feeding mothers ofanimals or humans with their sucking babies at risk of suffering ordeveloping harmful antibody-inducible diseases or conditions asmentioned above.

Wherein, the pharmaceutical compositions or the therapeutic products canbe provided to a biological organism including the feeding mothersmentioned above by a variety of routes such as subcutaneous, topicalwith or without occlusion, oral, intramuscular, intravenous (both bolusand infusion), intraperitoneal, intracavity, or transdermal, inhalant,or other using forms well known to those of ordinary skill in thepharmaceutical arts.

For example, injection of human immunoglobulin or healthy human serum orplasma to mouse pups before or after an influenza viral infection with ahighly pathogenic influenza viral strain reduced about 50% of the deathsof the mice with the infection (Table 7), as described in theexemplification.

Another aspect of the present invention discloses immunoglobulinproducts or serum or plasma and the methods of using the immunoglobulinproducts or the serum or the plasma to prevent and treat serious adversereactions of vaccines through vaccine-inducible antibodies. For example,injection of human immunoglobulin or human serum or human plasma topregnant mice prevented fatal and neonatal deaths (Tables 5-6),abortion, immature or delayed delivery of the dames, caused by theantibodies induced by influenza vaccines as described in theexemplification.

Another aspect of the present invention discloses immunoglobulinproducts or serum or plasma and the methods of using the immunoglobulinproducts or the serum or the plasma to prevent and treat to prevent andtreat fetal and neonatal deaths caused by infections or vaccines.

Another aspect of the present invention discloses the methods of usinghuman immunoglobulin products to prevent and treat infection-relatingautoimmune diseases, allergy and inflammation.

Another aspect of the present invention discloses the methods of usinghuman immunoglobulin products or human serum to prevent and treatinfection-relating inflammation.

For therapeutic use as mentioned above, the effective dosage amounts ofa serum or a plasma are from about 0.1 ml/kg to 100 ml/kg; the effectivedosage amounts of a human Ig products are from about 1 mg/kg to 100mg/kg.

Numerous other features or characteristics of therapeutic targets canbecome readily apparent from the detailed description.

A method of making better human immunoglobulin or antibody products

One embodiment of the present invention discloses methods of makingbetter human immunoglobulin products by mixing an immunoglobulin productor a therapeutic antibody with certain amount of N-acetylneuraminicacid, or an analog of N-acetylneuraminic acid (e.g. N-acetylneuraminicacid methyl ester) or N-acetylneuraminic acid plus an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester)

The effective amount or concentration of N-acetylneuraminic acid or ananalog of N-acetylneuraminic acid (e.g. N-acetymeuraminie acid methylester) are from 0.01 mg/g or 0.01 mg/ml to 100 mg/g or 100 mg/g.

Methods of Combination Use of Sialic Acid and Human Immunoglobulin orSerum or Plasma Products

One embodiment of the present invention discloses methods of usingimmunoglobulin or serum or plasma products at the time of administrationby mixing an immunoglobulin product or a therapeutic antibody withcertain amount of N-acetylneuraminic acid, or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) orN-acetylneuraminic acid plus an analog of N-acetylneuraminic acid (e.g.N-acetylneuraminic acid methyl ester), and administrate the mixture to asubject.

For therapeutic use as mentioned above, the effective dosage amounts ofa serum or a plasma are from about 0.1 ml/kg to 100 ml/kg; the effectivedosage amounts of a human Ig products are from about 0.1 mg/kg to 100mg/kg. The effective dosages of N-acetylneuraminic acid or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) arefrom 0.1 mg/kg to 100 mg/kg.

A method of making better human immunoglobulin or antibody products

One embodiment of the present invention discloses methods of makingbetter human immunoglobulin products at time of manufacturing by mixingan immunoglobulin or a serum or a plasma product or a therapeuticantibody with certain amount of N-acetylneuraminic acid, or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) orN-aeetymeuraminic acid plus an analog of N-acetylneuraminic acid (e.g.N-acetylneuraminic acid methyl ester}

The effective amount or concentration of N-acetylneuraminic acid or ananalog of N-acetylneuraminic acid (e.g. N-aeetymeuraminic acid methylester) are from 0.01 mg/g or 0.01 mg/ml to 100 mg/g or 100 mg/g.

Methods of Using Pathogens or Vaccines for Disorders Inducible byHarmful Antibodies

A vaccine or an inactivated pathogen can be used as a therapeutic drugfor the treatment of a severe infection caused by antibodies inducedduring an infection. The possible action mechanism of the therapeuticvaccines or inactivated pathogens is neutralization of harmfulantibodies.

Specific Antibodies for Infection-Relating Diseases or Conditions

One embodiment of the present invention discloses antibodies specific toa first pathogen to be used for preventing and treating an infectioncaused by a second pathogen. The present invention also discloses themethods of using the specific antibody products for preventing andtreating diseases and conditions relating to an infection. An antibodyproduct comprises at least one of an immunoglobulin molecule or animmunologically active portion of an immunoglobulin molecule.

One aspect of the present invention discloses antibodies specific to afirst pathogen (e.g. HAV or HBV or RSV) to be used for preventing andtreating diseases or conditions caused by a second pathogen (e.g. aninfluenza virus).

Wherein, the amounts or concentrations of an antibody specific to afirst pathogen are from about 0.001 gram (g) to about 100 g. Wherein theantibodies are in a form of a solution, a lyophilized, an injectable, aninfusion, or a form conjugated to a nano-particle, or other using formswell known to those of ordinary skill in the relevant arts.

Wherein, the antibodies specific to a first pathogen are used forpreventing or treating the diseases or conditions caused by a secondpathogen. The diseases or conditions include but not limited toinfectious diseases, serious adverse reactions of vaccines ortherapeutic antibodies, infection-relating autoimmune diseases,allergies, inflammation, infection-relating tumors, and other disorders(known or unknown) as mentioned above.

Another embodiment of the present invention discloses the methods ofusing an antibody specific to a first pathogen and treating the diseasesor conditions caused by a second pathogen. The diseases or conditionsinclude but not limited to infectious diseases, serious adversereactions of vaccines or therapeutic antibodies, infection-relatingautoimmune diseases, allergies, inflammation, infection-relating tumors,and other disorders (known or unknown) as mentioned above.

One aspect of the methods is consisted administrate an antibody specificto a first pathogen to a human or an animal individual at risk ofsuffering or developing diseases or conditions caused by a secondpathogen.

Another aspect of the methods is consisted of administrate an antibodyspecific to a first pathogen to the feeding mothers of animals or humanswith their sucking babies at risk of suffering or developing an diseasesor conditions caused by a second pathogen.

Wherein, the pharmaceutical compositions or the therapeutic products canbe provided to a biological organism including the feeding mothersmentioned above by a variety of routes such as subcutaneous, topicalwith or without occlusion, oral, intramuscular, intravenous (both bolusand infusion), intraperitoneal, intracavity, or transdermal, inhalant,or other using forms well known to those of ordinary skill in thepharmaceutical arts.

For example, injection of human anti-HAV or -HBV or -RSV or rotavirusantibody to mouse pups before or after an influenza viral infection witha highly pathogenic influenza viral strain reduced about 50% of thedeaths of the mice with the infection (Table 8), as described in theexemplification. Other examples include but not limited to:

a. Anti-HINI viral antibodies for protecting infections of H1N1, H3N2 orH5N1 virus;b. Anti-H3N2 viral antibodies for protecting infections of H 1N1 andH3N2 virus:c. Anti-H5N1 viral antibodies for protecting infections of H1N1, H3N2and H5N1 virus;d. Anti-respiratory syncytial viral antibodies for protecting infectionsof influenza viruses and respiratory syncytial vims;e. Anti-hepatitis A viral antibodies for protecting infections ofinfluenza viruses and hepatitis A virus;f. Anti-adeno virus antibodies for protecting infections of influenzaviral infections; org. Anti-rotavirus antibodies for protecting infections of influenzavirus

Another aspect of the present invention discloses the methods of usingan antibody specific to a first pathogen to prevent and treatinfection-relating autoimmune diseases, allergy and inflammation causedby a second pathogen.

Another aspect of the present invention discloses the methods of usingan antibody specific to a first pathogen to prevent and treatinfection-relating inflammation caused by a second pathogen.

As described above and in exemplification (Table 5, 6, 7), low dose offollowing immune sera or antibodies can be used as therapeutics forantibody-prevention and antibody-therapy of influenza infections.

-   -   a. Anti-seasonal H1N1 virus antibodies for the prevention of the        2009H1N 1 (swine), other H1N1 and H5N1 influenza vims infection;    -   b. Anti-2009H1N1 (Swine) vims antibodies for the prevention of        the other HΓN1 and H5N1 influenza virus infection; and    -   c. Anti-H5N1 vims antibodies for the prevention of a HΓN 1        influenza vims infection.

For therapeutic uses as mentioned above, the effective dosage amounts ofan antibody-specific to a first pathogen are from about 0.001 ml/kg to100 ml/kg.

Numerous other features or characteristics of therapeutic targets canbecome readily apparent from the detailed description.

In Vivo Proof of a Novel Action Mechanism of Vaccination and Antibodies

One embodiment of the present invention discloses a new functionalmechanism of vaccines and anti-pathogen antibodies. The antibodiesinduced by an infection or a vaccine or acquired through passiveimmunity bind to and block at least one binding site of a pathogen.

Another experimental model is developed by injecting an anti-firstpathogen antibody to an animal followed by infecting the animal with asecond infectious pathogen as described in exemplification. Theexperimental models can be used but not limited for the screening andidentifying shared binding sites by different pathogens, screening andtesting new vaccines which is made of a first pathogen and protect theinfection caused by a second pathogen. For example, the vaccines of HAV,HBV, RSV, rotavirus can be used for the prevention of influenzainfection as described in exemplification.

An experimental model is developed by injecting an anti-first pathogenantibody to an animal followed by infecting the animal with a secondinfectious pathogen as described in exemplification. For example, day 5mouse pups were injected separately with antibodies against HAV, HBV,RSV, adenovirus and rotavirus, followed by being infected with theA/PR/8/34(H1N1) influenza vims next day. Compared to the mouse pupspre-treated with saline, the mouse pups pre-treated with antibodiesagainst HAV, HBV, RSV, adenovirus and rotavirus were not or lightlyinfected with the influenza vims. All the antibodies did not react withthe influenza virus thus it was impossible for those antibodiesfunctioning by neutralization of the influenza virus. The only possibleaction mechanism of the antibodies against a different pathogen (e.g.HAV) was blocking a shared viral binding site with the influenza virus.

This experiment discovered not only a new mechanism of vaccines orpathogen inducible antibodies, but also a new kind of vaccines which ismade of a first pathogen and induce the antibodies which protect theinfection caused by a second pathogen; or a new kind of antibodiesspecific to a first pathogen which can protect the infection caused by asecond pathogen. Numerous other features or characteristics of such newtherapeutics and the uses thereof can become readily apparent from thedetailed description.

The experimental models can be used but not limited for the screeningand identifying shared binding sites by different pathogens, screeningand testing new vaccines which is made of a first pathogen and induceantibodies capable of protecting the infection caused by a secondpathogen. For example, the vaccines of HAV, HBV, RSV, rotavirus can beused for the prevention of influenza infection as described inexemplification.

New Vaccines for Infectious Disease

One embodiment of the present invention discloses vaccines comprising afirst pathogen which induces antibodies capable of protecting aninfection caused by a second pathogen. The present invention alsodiscloses the methods of using the specific vaccine made of the firstpathogen capable of inducing antibodies for preventing and treatingdiseases and conditions relating to an infection caused by a secondpathogen.

One aspect of the present invention discloses the vaccines comprising afirst pathogen (e.g. HAV or HBV or RSV) and induce antibodies capable ofpreventing and treating diseases or conditions caused by a secondpathogen (e.g. an influenza vims).

Wherein, the vaccines comprising a first pathogen are used forpreventing or treating the diseases or conditions caused by a secondpathogen. The diseases or conditions include but not limited toinfectious diseases, serious adverse reactions of vaccines ortherapeutic antibodies, infection-relating autoimmune diseases,allergies, and inflammation, and infection-relating tumors, and otherdisorders (known or unknown) as mentioned above. Another embodiment ofthe present invention discloses the methods of using an antibodyspecific to a first pathogen and treating the diseases or conditionscaused by a second pathogen. The diseases or conditions include but notlimited to infectious diseases, serious adverse reactions of vaccines ortherapeutic antibodies, infection-relating autoimmune diseases,allergies, and inflammation, and infection-relating tumors, and otherdisorders (known or unknown) as mentioned above.

One aspect of the methods is consisted of administrating a vaccinescomprising a first pathogen to a human or an animal individual at riskof suffering or developing diseases or conditions caused by a secondpathogen.

Another aspect of the methods is consisted of administrating vaccinescomprising a first pathogen to the feeding mothers of animals or humanswith their sucking babies at risk of suffering or developing an diseasesor conditions caused by a second pathogen.

Wherein, the pharmaceutical compositions or the vaccines can be providedto a biological organism including the feeding mothers mentioned aboveby a variety of routes such as oral, intramuscular, inhalant, or otherusing forms well known to those of ordinary skill in the pharmaceuticalarts.

New Methods of Use with Influenza Vaccines

One embodiment of the present invention discloses methods of usinginfluenza vaccines. As described in exemplification, the influenzavaccine-induced anti-2009H1N1 (swine) and anti-H5M 1 immune sera(pre-treated with NeuSAc) were effective for prevention and treatment ofthe A/PR″8/34(H1N1) virus infection in mouse pups (Tables 6-7). Theseresults provide in vivo evidence that two different influenza viruses(e.g. 2009H1N1 and H5N1 virus) can share at least one binding site. Thusblocking the shared binding site by a antibody induced by either viruscan prevent and treat not only the infection of the virus (e.g. a H5N1virus) but also the infection of the other virus (e.g. a H1N1 virus).

Another embodiment of the present invention is disclosing the methods ofusing a vaccine comprising one viral strain (e.g. the 2009H1N1 swinevims) for preventing the infections of a different viral strain (e.g.A/PR/8/34H1N1 virus or a H5N1 vims). One aspect of the present inventiondisclose following new vaccines based on the shared binding sites.

-   -   a. A vaccine comprising a H1N1 viral strain for the prevention        of the infections of a different H1N1 virus or a H5N1 virus: and    -   b. A vaccine comprising a H5N1 virus for the prevention of the a        H1N1 influenza infection.

Other example of the vaccines include but not limited to:

a. A vaccine comprising a H1N1 influenza virus for protection of H3N2 orH5N1 viral infection;b. A vaccine comprising a H3N2 influenza virus for protection of H1N1viral infection;c. A vaccine comprising a H5N1 influenza virus for protection of H1N1 orH3N2 viral infection;d. A vaccine comprising a respiratory syncytial virus for protection ofinfluenza viral infections;e. A vaccine comprising a hepatitis A virus for protection of influenzaviral infections;f. A vaccine comprising a adenovirus for protection of influenza viralinfections; org. A vaccine comprising a rotavirus for protection of influenza viralinfections.Another aspect of the present invention discloses the methods of using avaccine comprising a first pathogen to prevent and treatinfection-relating autoimmune diseases, allergy and inflammation causedby a second pathogen.

For therapeutic use as mentioned above, the effective dosage amounts ofa vaccine comprising to a first pathogen are at a amount to induce lowto moderate levels of antibodies. Numerous other features orcharacteristics of therapeutic targets can become readily apparent fromthe detailed description.

Another embodiment of the present invention discloses a vaccine or aninactivated pathogen which can be used as a therapeutic for thetreatment of a severe infection caused by antibodies induced during aninfection. Another aspect of the invention is to disclose the methods ofadministrate a therapeutic product comprising a vaccine or aninactivated pathogen to a patient to prevent or treat the disorders orconditions caused by the antibodies against the vaccine or the pathogeninduced during an infection. The possible action mechanism of thetherapeutic vaccines or inactivated pathogens is neutralization ofharmful antibodies.

Methods of Combination Use of Sialic Acid and Other Therapeutic Products

One embodiment of the present invention discloses methods of thecombination uses of N-acetylneuraminic acid with other therapeuticproducts such as but not limited to immunoglobulin or serum or plasmaproducts or antibody products at the time of administration by mixingsuch a therapeutic product with certain amount of N-acetylneuraminicacid, or an analog of N-acetylneuraminic acid (e.g. N-acetylneuraminicacid methyl ester) or N-acetylneuraminic acid plus an analog ofN-acetylneuraminic acid (e.g. N-aeetymeuraminic acid methyl ester), andadministrate the mixture to a subject.

As described in exemplification, and shown in Tables 6-8, thecombination uses of N-acetylneuraminic acid with non-specific humanserum, or non-specific human immunoglobulin, or specific anti-influenzaantibodies, or a specific antibody to a non-influenza virus aresignificantly effective for the prevention of the H IN 1 influenzainfection. The data indicated that N-acetylneuraminic acid significantlyincreased the anti-infection efficacy of the non-specific human serum,or the non-specific human immunoglobulin, or the specific anti-influenzaviral antibodies or the specific antibodies to a pathogen different froman influenza pathogen, and decreased the toxicity of a specific harmfulantibody (e.g. an anti-influenza viral antibody).

For example, the anti-2009H1N1 (Swine), anti-seasonal-H IN 1, andanti-H5N1 viral immune sera pre-mixed with N-acetylneuraminic acidshowed best efficacy and lowest toxicity for prevention and treatment ofinfluenza infections caused by A/PR/8/34(H 1N1) virus in newborn mice(Table 6 and 7) as described in exemplification.

Another example as described in exemplification (Table 5), injectionwith moderate or high dose of antibodies against 2009H 1N1 (swine),seasonal H1N1, avian H5N1 and B influenza viruses into chicken embryo atday 16 and day 19 induced the leg disability of newborn chicks which issimilar to the Guillain-Barre syndrome (GBS) in human. However, newbornchicks with injection of the same antibodies pre-mixed withN-acetylneuraminic acid (NeuSAc) did not develop the GBS-like condition(Table 5).

Another example as described in exemplification (Tables 5-7), thenewborn mouse pups delivered to the dames treated with injection of theimmune sera containing moderate to high dose of antibodies against2009H1N1 (swine), seasonal H1N1, avian H5N1 and B influenza vims atembryo day 16 and 19 were sick or died; the newborn pups with injectionof the immune sera mixture with N-acetylneuraminic acid did notdeveloped disorders.

For such therapeutic uses as mentioned above, the effective dosageamounts of a serum or a plasma are from about 0.1 ml/kg to 100 ml/kg;the effective dosage amounts of a human Ig products are from about 0.1mg/kg to 100 mg/kg. The effective dosages of N-acetylneuraminic acid oran analog of N-acetylneuraminic acid (e.g. N-acetylneuraminic acidmethyl ester) are from 0.1 mg/kg to 100 mg/kg.

The possible action mechanism of N-acetylneuraminic acid is targetingharmful antibodies, thus it is effective as a drug one week after avaccination or a viral infection.

Numerous other features or characteristics of therapeutic targets canbecome readily apparent from the detailed description.

EXEMPLIFICATION 1. Antibodies and Therapeutics

1.1 Following Immune Sera were Tested as Described Below.

-   -   a. Human immune plasma from three individuals immunized with the        influenza vaccine made of the 2009Fl1N1 influenza virus (swine)        and another three individuals naturally infected with the        2009H1N1 influenza virus (swine) (National influenza Center of        China CDC).        -   Antibody titers: 1:128-1:1280 (all adjusted to 1:128).    -   b. Human immune sera from five individuals with natural        infection of the 2009H 1N 1 influenza virus (swine) (National        influenza Center of China CDC).        -   Antibody titers: 1:80-1:160 (all adjusted to 1:80).    -   c. Human immune sera from five individuals naturally infected        with seasonal HΓN 1 influenza viruses (Guangdong/Baoan/2006,        Guangdong/Luohu/2008, Tianjin/2009) (National influenza Center        of China CDC).        -   Antibody titers: 1:64-1:520 (all adjusted to 1:128 if            possible).    -   d. Human immune sera from three individuals with natural        infection of a H3N2 influenza virus (Brisbane/59/Xinjiang/2007)        (National influenza Center of China CDC).        -   Antibody titers: 1:1280 (ail adjusted to 1:128).    -   e. Human immune serum from three individuals natural infected        with a H5N1 (avian) influenza virus (Anhui, 2005) (National        influenza Center of China CDC).        -   Antibody titers: 1:64-1:512 (all adjusted to 1:128 if            possible).    -   f. Human immune serum from three individuals natural infected        with a B influenza virus (Florida/4/Y unnan/2007) (National        influenza Center of China CDC).    -   g. Human serum or plasma pool consisted of sera or plasma from        ten healthy individuals without infection or vaccination of        influenza viruses.        -   Antibody titers to a seasonal H 1N 1 virus: 1:5.

1.2 Following Products were Tested as Described Below.

-   -   a. Human serum or plasma pool is as described above.    -   b. A commercially available purified human immunoglobulin (Ig)        (10%).    -   c. A formulations comprising N-acerylneuraminic acid (1 mg/ml).

1.3 Following Serum Mixtures were Prepared as Described Below.

-   -   a. Each 100 microliter of the human anti-09H1N1 (swine),        anti-H1N1 (seasonal) and anti-H5N1 (avian) sera were mixed with        each 100 microliter of the human serum pool    -   b. Each 100 microliter of the human anti-09H1N1 (swine),        anti-H1N1 (seasonal) and anti-H5N1 (avian) sera were mixed with        each 100 micrograms of the human Ig.        -   Each 100 microliter of the human anti-09H1N1 (swine),            anti-H1N1 (seasonal) and anti-H5N1 (avian) sera were mixed            with each 100 microliter of the formula comprising            N-acetylneuraminic acid as mentioned above.

2. Experimental Models for Evaluating the Safety of Vaccines andAntibodies

2.1 an Animal Model of Chicken Embryos and Newborn Chicks

Chicken embryos were treated via ailantois injection of various humananti-influenza viral immune sera or other anti-pathogen antibodies atday 16 (E16) and 19 (E19) and the healthy status of the newborn chickswere observed. The chicks were born at about E21.

Eight groups of chicken embryos were treated at day 16 (E16) and 19(E19) via ailantois injection of each 100 microliter of 1) saline alone(n=20): 2) the human serum pool as mentioned above (n=20); 3) humanserum from a RSV infected subject (n=20}: 4) the human anti-2009H1N1(swine) sera (n=40); 5) the human anti-seasonal H1N1 serum (n=40); 6)the human anti-H3N2 sera (n=40): 7) the human anti-H5N1 (avian) serum(n=40); and 8) the human anti-B viral sera (n=40). The chicken embryoswere kept culturing in a 35° C. incubator until the newborn chicks wereborn at about E21.

Injection of the anti-2009H1 N1 sera, the anti-seasonal H5N1 (avian)sera and the anti-B sera as described above induced the leg disabilityof newborn chicks which is similar to the Guillain-Barre syndrome (GBS)in humans. The frequencies of GBS-like condition induced by theanti-influenza virus antibodies are listed in Table 1. The resultsindicated that the antibodies induced by the 2009H1N1 (swine) virus orthe vaccine comprising the 2009H1N1 (swine) virus is at highest risk forinducing GBS-like disorders, followed by antibodies induced by the avianH5N1 (avian) virus and the influenza B virus. However, with reduceddosages (50 microliter or less), none of the sera induced significantdisorders with the chicks treated with the antibody injections. The dataindicated that moderate or high dose of anti-H1N1 (swine), anti-H5N1 andanti-B antibodies can induce serious adverse reactions of chickenembryos and newborn chicks.

TABLE 1 The frequency of GBS-like condition of newborn chicks withantibody injection Odds Human immune serum n = GBS (%) Ratio 95% CI PSaline 20 0 (0.00) Infinity Infinity Infinity Normal seral pool* 20 0(0.00) Infinity Infinity Infinity Anti-RSV 20 0 (0.00) Infinity InfinityInfinity Anti-HlNl/09 (swine)* 40 17 (42.5)  28.8 3.60-231 <.0001Anti-HIN1/seasonal 40 7 (17.5) 8.27  0.97-70.7 0.06 Anti-H3N2 40 6(15.0) 6.88  0.79-60.1 0.11 Anti-H5NI 40 11 (27.5)  14.8 1.81-121 0.003Anti-B 40 13 (32.5)  18.8 2.32-152 0.0007 *Serai pool often healthyindividuals without infection or vaccination of influenza viruses **:Sera from subjects with either natural infection or vaccination of the2009H1N1 influenza virus RSV = Respiratory Syncytial Viruses; GBS =Guillain-Barre syndromeIn addition, injection of human anti-influenza viral sera induced fetaland neonatal deaths of the chicken embryos or newborn chicks. The deathrates are listed in Table 2. The results with this animal modelindicated that the antibodies induced by the B influenza virus is at thehighest risk for inducing fetal and neonatal deaths (65.0%), followed bythe antibodies induced by the avian H5N1 virus (57.5%), 2009H1N1 (swine)virus (52.5%), the H3N2 virus (37.5%) and the seasonal H1N1 virus(15.0%). As a control, the anti-respiratory syncytial viruses (RSV)serum did not cause significant GBS-like conditions nor deaths (Tables1-2).

TABLE 2 The death frequecies of newborn chicks with antibody injectionOdds Human immune serum n = Death* (%) Ratio 95% CI P* Normal serai pool40  3 (7.50) 1.54 0.15-15.8 1.00 Anti-RSV 20  1 (5.00) 0.65 0.06-6.671.00 Anti-HlNi/09 (swine) 40 21 (52.5) 13.6 3.60-51.6 <.0001Anti-HIN1/seasonal 40 12 (30.0) 5.29 1.36-20.5 0.02 Anti-H3N2 40 15(37.5) 7.40 1.94-28.2 0.002 Anti-H5N1 40 23 (57.5) 14.7 4.40-63.3 <.0001Anti-B serum 40 26 (65.0) 22.9 5.97-87.8 <.0001 Anti-H1N109+Neu5Ac 20  3(15.0) 0.16 0.04-0.63 0.01 Neu5Ac Anti-HINI + Neu5Ac 20  1 (5.00) 0.120.02-1.02 0.04 Anti-H5N1 + Neu5Ac 20  2 (10.0) 0.08 0.02-0.41 0.0006*Including fetal and neonatal deathIn another experiment, the serum mixtures as prepared above in 1.3 werealso tested using the animal model Compared to injections of eachanti-influenza viral serum alone, injection of the serum mixtures asmentioned above significantly reduced the GBS-like conditions or deaths(Tables 2) of the newborn chicks. A formula comprisingN-acetylneuraminic acid methyl ester as an analog of N-acetylneuraminicacid was also tested with the method using N-acetylneurammic acid asmentioned above. The results were similar to the results ofN-acetylneuraminic acid as shown in Table 2.

The effective dosages of N-acetylneuraminic acid or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) arefrom 0.1 mg/kg to 100 mg/kg.

2.2 an Animal Model of Pregnant Mice

Pregnant mice were treated twice via intraperitoneally (IP) injection ofvarious human anti-influenza viral immune sera or other anti-pathogenantibodies at pregnancy day E16 and E19 respectively. The mouse pupswere bora at about E21 and the healthy status of the newborn mouse pupswere observed.

As shown in Table 3-4, injection of the human anti-influenza viral serainto pregnant mice at pregnant day 16 (E16) and E19 induced abortion ofthe pregnant mice, immature or delayed delivery, and fatal and neonataldeath of the newborn mouse pups delivered to the dames. The frequenciesof fatal and neonatal death of the newborn mouse pups are listed inTable 3. The results with this animal model indicated that theantibodies induced by the H5N 1 (avian) virus is at the highest risk forinducing death (34.6%), followed by the antibodies induced by theseasonal H1N1 virus (26.7%), and the H3N2 virus (26.5%), B influenzavirus (23.5%), and the 2009H1N1 (swine) virus (22.9%).

TABLE 3 The death rates of mouse fetus or newborns with anti-influenzaserum injection Odds Human Serum N= Deaths Rate(%) Ratio 95% CI P valueNormal serai 53 3 5.66 1.03 0.10-10.7 1.00 pool Anti-RSV 18 1 6.70 0.790.08-8.22 1.00 Anti-09H1N1 83 19 22.9 4.95 1.39-17.7 0.008 (swine)Anti-H1N1 75 20 26.7 6.06 1.69-21.6 0.002 (seasonal) Anti-H3N2 68 1826.5 6.00 1.66-21.7 0.003 Anti-H5N1 133 46 34.6 8.81 2.61-29.8 <.0001Anti-B 85 20 23.5 5.13 1.44-18.2 0.009

The frequencies of abortion of the pregnant mice are listed in Table 4.The results with this animal model indicated that the antibodies inducedby the B influenza virus is at the highest risk for inducing abortion(33.3%), followed by the antibodies induced by the 2009H1N1 (swine)virus (31.3%), the H3N2 virus (28.6%), the seasonal H1N1 virus (21.4%),and the H5N1 (avian) virus (20.0%).

TABLE 4 The abortion frequeeies of pregnant mice with anti-influenzaserum injection Abor- Odds Human Serum N= tion Rate (%) Ratio 95% CT PNormal serai 15 1 6.67 0.48 0.04-5.40 0.60 pool* Anti-09H1N1 16 5 31.36.36 0.65-62.7 0.18 (swine) Anti-HINI 14 3 21.4 3.82 0.35-42.0 0.33(seasonal) Anti-H3N2 14 4 28.6 7.78 0.78-77.9 0.08 Anti-H5N1 20 4 20.03.50 0.35-35.1 0.36 Anti-B 15 5 33.3 7.00 0.71-69.5 0.17 Anti-RSV 3 00.00 Infinity Infinity Infinity

The histology changes of the dead mice showed that the infiltration withred blood cells, inflammatory cells and proliferation of epitheliumcells, and local tissue lesions were observed in the tissues of lung(FIG. 1), brain, heart and liver of the dead chicks and mouse pups. Inaddition, binding of human IgG to those organs was detectable with thetissue sections of the dead chicks and mouse pups (data not shown).

Taken together, the present invention discloses a direct evidence forthe first time that high levels of antibodies against influenza virusesare toxic to fetuses and newborns. According to our knowledge, this isthe first direct proof of the association of influenza vims-inducibleantibodies with the serious adverse reactions such as GBS-like conditionand fetal or neonatal deaths. This finding suggests that vaccinatingpregnant mothers with influenza vaccines may^(¬)be risky for the fetusesand newborns. 3. Products for prevention and treatment of disordercaused by harmful antibodies

3.1 Therapeutics for Preventing and Treating Fetal and Neonatal Deaths

The serum mixtures as prepared above in 1.3 were injectedintraperitoneally twice to pregnant mice at pregnancy day E16 and E19respectively. The mouse pups were born at about E21 and the healthystatus of the newborn mouse pups were observed.

Compared to injections of each anti-influenza viral serum alone,injection of the serum mixtures as mentioned above to pregnant miceprevented fatal and neonatal deaths of those dames (Tables 5). Inaddition, no significant abortion, immature or delayed delivery of thedames treated with the serum mixtures were observed. A formulacomprising N-acetylneurammic acid methyl ester as an analog ofN-acetylneuraminic acid was also tested with the method usingN-acetylneuraminic acid as mentioned above. The results were similar tothe results of N-acetylneuraminic acid as shown in Table 5.

TABLE 5 Therapeutics for preventing fetal and neonatal deaths caused byinfluenza antibodies Odds Human Serum N= Deaths Rate(%) Ratio 95% CI Pvalue Seram pool (SP) 53 3 5.66 1.03 0.10-10.7 1.00 Human Ig (H-lg) 20 15.00 0.88 0.09-8.96 1.00 Anti-09H1N1 (swine) 83 19 22.9 4.95 1.39-17.70.008 Anti-09H1N1 + SP 20 1 5.00 0.18 0.02-1.41 0.11 Anti-09H1N1 + H-lg22 1 4.55 0.16 0.02-1.27 0.06 Anti-09HlNl + Neu5Ac 26 2 7.69 0.28.006-1.30 0.09 Anti-HINI (S) 75 20 26.7 6.06 1.69-21.6 0.002Anti-HINIS + SP 18 1 5.56 0.16 0.12-1.29 0.06 Anti-H1N1S + H-lg 21 i4.76 0.14 0.17-1.09 0.04 Anti-HlNlS + Neu5Ac 23 1 4.35 0.12 0.13-0.990.04 Anti-H5N1 133 46 34.6 8.81 2.61-29.8 <.0001 Anti-H5N1 + SP 21 29.52 0.20 0.04-0.89 0.02 Anti-H5N1 + H-lg 23 2 8.70 0.18 0.04-0.80 0.01Anti-H5N 1 + Neu5Ac 28 3 10.7 0.23 0.07-0.79 0.01 Note: SP = Serum Pool;Ig = Immunoglobulin: NeuSAc = N-acetylneuraminic acid; S = Seasonal; H =Human.

Based on the data and observations, following products are effective forpreventing or treating the disorders or conditions (e.g. GBS-likecondition, fetal or neonatal death) caused by harmful antibodies: 1) thenon-specific sera of healthy individuals; 2) human immunoglobulin; and3) N-acetylneuraminic acid or an analog of N-acetylneuraminic acid (e.g.N-acetylneuraminic acid methyl ester).

For preventing or treating the disorders or conditions (e.g. GBS-likecondition, fetal or neonatal death) caused by harmful antibodies asmentioned above, the effective dosage amounts of a serum or a plasma arefrom about 0.1 ml/kg to 100 ml/kg; the effective dosage amounts of ahuman Ig products are from about 0.1 mg/kg to 100 mg/kg: the effectivedosages of N-acetylneuraminic acid or an analog of N-aeetyineuraminicacid (e.g. N-acetylneuraminic acid methyl ester) are from 0.1 mg/kg to100 mg/kg.

3.2 Therapeutics for Treating Influenza Infection

Ten groups of newborn bulb/c pups were inoculated at day 5 (P5) via oraland nasal administration of 30 μT (microliter} of the A/PR/8/34(H1N1)influenza virus (titer: 1:512, diluted 100 times with saline}; and weretreated at day 6 (P6) via intraperitoneal injection with 100 microliterof saline containing 1) saline alone; 2) 100 microliter of the humanserum pool: 3) 100 micrograms of the human Ig; 4) 30 microliter of thehuman anti-2QQ9H1N1 (swine) semm; 5) 30 microliter of the humananti-H1N1 serum; 6) 30 microliter of the human anti-H5N1 serum; 7) amixture of 30 microliter of the human anti-2009H1N1 (swine) serum plus100 micrograms of N-acetylneuraminic acid (NeuSAc); 8) a mixture of 30microliter of the human anti-H5N1 serum plus 100 micrograms of NeuSAc;9) a mixture of 100 microliter of the human semm pool plus 100micrograms of NeuSAc; and 10) 100 micrograms of the human Ig plus 100micrograms of NeuSAc. Mice were kept for 7 days after infection.

TABLE 6 Therapeutics for treating influenza infection of A/PR/8/34(HlNl)virus Odds Human Serum n= Death Death (%) Ratio 95% CI P Saline 20 1787.0 6.67 1.53-29.1 0.02 Serum pool (10) 22 11 50.0 0.17 0.04-0.78 0.02Human Ig 21 9 42.9 0.13 0.01-0.41 0.001 Anti-09H1N1 (swine) 13 13 100Infinity Infinity Infinity Anti-H1N1 (seasonal) 15 15 100 InfinityInfinity Infinity Anti-H5Nl (avian) 13 6 46.2 0.15  .03-0.78 0.03Anti-09HlNl + Neu5Ac 22 4 18.2 0.04 .008-0.20 <.0001 Anti-H5N 1 + Neu5Ac21 4 19.1 0.04 .008-0.21 <.0001 Serum pool + Neu5Ac 21 6 28.6 0.070.02-0.33 0.0009 Human Ig + Neu5Ac 20 5 25.0 0.06 0.01-0.29 0.0003 Note:Ig = Immunoglobulin; NeuSAc = N-acetylneuraminic acid: S = Seasonal.

As summarized in Table 6, 17/20 (87%) of the pups treated with saline,and all (100%) of the pups treated with the anti-2009H1N1 serum alone orthe anti-seasonal H1N 1 semm alone died at day 3 after viral infection.50% or more of the pups treated with the human serum pool (50%) or thehuman Ig (57.1%) or the anti-H5N1 serum survived. The death rates of thepups treated with the serum mixtures with N-aeetymeuraminic acid weresignificantly reduced (Table 6). The results indicated thatN-acetylneuraminic acid can significantly reduce the toxicity of theharmful antibodies or increase the efficacy of the human Ig or humanserum or plasma for the treatment of an serious influenza infection. Thedata also suggested that high dose of the anti-20QQ9H1N1 (swine)antibodies alone are harmful rather than helpful for the treatment of aninfluenza infection.

For treating influenza infections, the effective dosage amounts of aserum or a plasma are from about 0.1 ml/kg to 100 ml/kg; the effectivedosage amounts of a human Ig products are from about 0.1 mg/kg to 100mg/kg; the effective dosages of N-acetylneurarainic acid or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) arefrom 0.1 mg/kg to 100 mg/kg.

3.3 Therapeutics for Preventing Influenza Infection

In another experiment using the mouse model mentioned above in 3.2, tengroups of newborn bulb/c mouse pups were pretreated at day 5 (P5) viaintraperitoneal injection with the sera and the serum mixtures asmentioned above in 3.2. The pups were inoculated at day 6 (P6) via oraladministration of 30 μT (microliter) of the A/PR/8/34(H1N1) virus(titer: 1:512, diluted 100 times with saline), and kept for 7 days afterviral infection.

The results are summarized in Table 7. The data indicated that I) thehuman serum pool or the human immunoglobulin alone or the anti-H5N1reduced the death rate of the A/PR/8/34(H1N1) infection from 87.0% to50% or 42.9% (1.74-2.0 folds); 2) the specific anti-seasonal H1N1 serumor the anti-2QQ9H1N1 (swine) serum (containing specific antibodies at atiter of 1:128) is not effective or harmful for the prevention of theA/PR/8/34(H 1N 1) infection; and 3) the combination uses ofN-acetylneuraminic acid with non-specific human serum, or non-specifichuman immunoglobulin, or specific anti-influenza antibodies andN-acetylneuraminic acid are significantly effective for the preventionof the H1N1 influenza infection; and 4) N-acetylneuraminic acidsignificantly increased the anti-infection efficacy of non-specifichuman semm, or non-specific human immunoglobulin, or specificanti-influenza viral antibodies, and decreased the toxicity of aspecific harmful antibody (e.g. an anti-influenza viral antibody).

TABLE 7 Therapeutics for preventing influenza infection ofA/PR/8/34(HlNl) virus Odds Human Serum n= Death Death (%) Ratio 95% CI PSaline 21 18 85.7 6.00 1.30-27.8 0.04 Serum pool (10) 18 9 50.0 0.170.03-0.77 0.04 Human Ig 20 9 45.0 0.14 0.03-0.62 0.001 Anti-09H1N1(swine) 12 12 100 Infinity Infinity Infinity Anti-HIN1 (seasonal) 11 11100 Infinity Infinity Infinity Anti-H5N1 (avian) 12 6 50.0 0.17.003-0.88 0.04 Anti-09HlNl + Neu5Ac 23 4 17.4 0.04 .007-0.18 <.0001Anti-H5Nl + Neu5Ac 21 3 14.3 0.03 .005-0.16 <.0001 Serum poo3 + Neu5Ac20 6 30.0 0.07 0.02-0.34 0.0004 Human Ig + Neu5Ac 23 6 26.1 0.060.01-0.27 <.0001 Note: Ig = Immunoglobulin; NeuSAc = N-acetylneuraminicacid; S = Seasonal

For preventing influenza infections, the effective dosage amounts of asemm or a plasma are from about 0.1 ml/kg to 100 ml/kg; the effectivedosage amounts of a human Ig products are from about 0.1 mg/kg to 100mg/kg; the effective dosages of N-acetylneuraminic acid or an analog ofN-acetylneuraminic acid (e.g. N-acetylneuraminic acid methyl ester) arefrom 0.1 mg/kg to 100 mg/kg.

3.4 Another Experimental Model

A mouse model is developed by injecting an anti-first pathogen antibodyto an animal followed by infecting the animal with a second infectiouspathogen.

Six groups of newborn bulb/c mouse pups were pretreated at day 5 (P5)via intraperitoneal injection with other antibodies to other pathogens,which did not react with an influenza virus as described below. The pupswere inoculated at day 6 (P6) via oral administration of 30 μl(microliter) of the A/PR/8/34(H1N1) virus (titer: 1:512, diluted 100times with saline), and kept for 7 days after viral infection. Thetested antibodies to other pathogens were:

a. The human immune sera from subjects infected with RSV:b. The human immune sera from subjects infected with HAV;c. The human immune sera from subjects infected with HBV;d. The human immune sera from subjects infected with rotavirus.

All the antibodies did not react with the influenza virus.

The results are summarized in Table 8. Compared to the mouse pupspre-treated with saline, the mouse pups pre-treated with antibodiesagainst HAV, HBV, RSV, and rotavirus were not or lightly infected withthe influenza virus. The data indicated that an antibody against a firstpathogen (e.g. HAV) can prevent an infection of a second pathogen.

In addition, the combination uses of N-acetylneuraminic acid with thosespecific antibodies to a pathogen different from an influenza pathogensignificantly increased the antibody efficacy for the prevention of theH1N1 influenza infection.

TABLE 8 Various antibodies for preventing influenza infection ofA/PR/8/34(H1N1) virus Odds Human Serum n= Death Death (%) Ratio 95% CI PSaline 20 18 90.0 9.00 1.60-50.7 0.01 Serum pool (10) 18 9 50.0 0.110.02-0.63 0.01 Anti-HINI(S) 12 11 91.7 1.22 0.10-15.1 1.00 Anti-RSV 14 17.14 0.01 .0007-0.10  <.0001 Anti-Rotavirus 11 2 18.2 0.03 .003-0.21<.0001 Anti-HAV 13 2 15.4 0.02 .0003-0.16  <.0001 Anti-HBV 12 3 25.00.04 .005-0.26 0.0003 Note: Neu5Ac = N-acetylneuraminic acid: S =Seasonal.

For preventing an influenza infections, the effective dosage amounts ofthe specific antibodies to a pathogen different from an influenzapathogen are from about 0.001 mg/kg to 100 mg/kg; the effective dosagesof N-acetylneuraminic acid or an analog of N-acetylneurammie acid (e.g.N-acetylneurammie acid methyl ester) are from 0.1 mg/kg to 100 mg/kg.

3.4 Combination Use of Therapeutic Antibodies with N-AcetylneurammieAcid

As mentioned above and shown in Tables 6-8, the combination uses ofN-acetylneuraminic acid with non-specific human serum, or non-specifichuman immunoglobulin, or specific anti-influenza antibodies, or aspecific antibody to a non-influenza virus are significantly effectivefor the prevention of the H1N1 influenza infection. The data indicatedthat N-acetymeuraminic acid significantly increased the anti-infectionefficacy of the non-specific human serum, or the non-specific humanimmunoglobulin, or the specific anti-influenza viral antibodies or thespecific antibodies to a pathogen different from an influenza pathogen,and decreased the toxicity of a specific harmful antibody (e.g. ananti-influenza viral antibody).

Additional Definitions

As used herein, the term “treating” or “treatment” refers to clinicalintervention (such as, e.g., administration of an immunoglobulinproduct, serum, or plasma, as described herein) designed to alter thenatural course of the individual or cell being treated during the courseof clinical pathology of a viral infection. Desirable effects oftreatment include decreasing the rate of disease progression ormortality, ameliorating or palliating the disease state, and remissionor improved prognosis. In some embodiments, the treatment improvessymptoms of viral infection (e.g., an influenza viral infection),reduces frequency or severity of the disease caused by the viralinfection (e.g., influenza), and/or improves patient-reported symptoms(e.g., such as symptoms of influenza, including, but not limited to,e.g., fever, chills, cough, sore throat, body aches, and fatigue). Aresponse is achieved when the patient experiences partial or totalalleviation, or reduction of signs or symptoms of illness, and, in someembodiments, includes survival. A subject is successfully “treated,” forexample, if one or more symptoms associated with a viral infection (suchas influenza) are mitigated or eliminated.

As used herein, the term “preventing” or “prevention” includes providingprophylaxis with respect to occurrence or recurrence of viral infection(such as influenza) in an individual. An individual may be predisposedto or susceptible to viral infection (such as infection by an influenzavirus}, but has not yet been infected with the virus.

As used herein, an individual “at risk” of viral infection (such asinfluenza infection) denotes that an individual is likely to be exposedto a viral pathogen or has one or more risk factors of having severereactions to viral pathogen if infected.

An “effective amount” refers to at least an amount of immunoglobulinproduct, serum or plasma, as described herein, that is effective, atdosages and for periods of time necessary, to achieve the desired orindicated effect, including a therapeutic or prophylactic result. Aneffective amount can be provided in one or more administrations.

As used herein, the term “patient” or “individuar refers to a mammal,including, but not limited to, a human or non-human mammal, such as abovine, equine, porcine, canine, ovine, or feline. In some embodiments,the patient or individual is a human. In some embodiments, the patientis not in need of a blood transfusion due to, e.g., an injury orbleeding clotting disorder such as, but not limited to, e.g.,hemophilia, von Willebrand disease, and leukemia.

In some embodiments, the patient and the healthy individual are bothhuman. In some embodiments, the patient and the healthy individual areboth cows, sheep, chickens, pigs, horses, dogs, or cats.

As used herein, the patient in the present invention comprises human ornon-human mammal of males and females, newborns, 1-12 months oldinfants, 1-18 years old, adults, pregnant and feeding females, andpregnant or feeding females with their fetus or sucking babies at riskof suffering or developing the diseases and conditions caused by harmfulantibodies.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is a graphical representation of histology changes of lungs fromthe mouse pups delivered to the dams treated with human serum of healthyindividuals (A) or the anti-09HIN1influenza virus serum (B). This datashowed that antibodies induced by the 09H 1N 1 influenza vims areharmful to fetuses and newborns since it caused later fetal death (stillbirth) and neonatal death.

ADDITIONAL EMBODIMENTS

Another embodiment of the present invention discloses therapeuticproducts comprising a vaccine or an inactivated pathogen for thetreatment of a severe infection caused by antibodies induced during aninfection; wherein the therapeutic vaccines or inactivated pathogensneutralize harmful antibodies induced during the infection.

Another embodiment of the present invention discloses a method ofadministrating a therapeutic vaccine or an inactivated pathogen to apatient to prevent or treat the disorders or conditions caused by theantibodies against the vaccine or the pathogen; wherein the antibodiesare induced during an infection; the therapeutic vaccines or inactivatedpathogens neutralize harmful antibodies induced during the infection.

Other embodiments besides the above may be articulated as well. Theterms and expressions therefore serve only to describe the disclosure byexample only and not to limit the disclosure. It is expected that otherswill perceive differences, which while differing from the foregoing, donot depart from the spirit and scope of the disclosure herein describedand claimed. All patents, patent publications, and other referencescited herein are incorporated herein by reference in their entirety.

1: A therapeutic product for treating and preventing an infection causedby a viral pathogen or a disease or condition caused by a harmfulantibody, comprising: (a) an N-acetylneuraminic acid; and (b) at leastone of a specific antibody to a viral pathogen, an immunoglobulin, andserum or plasma, wherein the harmful antibody is induced by aninfection, a vaccination, or a passively introduced therapeuticantibody, wherein the disease or condition caused by the harmfulantibody comprises an infectious disease, a serious adverse reaction toa vaccine or a therapeutic antibody, an infection-related autoimmunedisease, an allergy, inflammation, or an infection-related tumor, andwherein the immunoglobulin, serum, or plasma is obtained from a healthyindividual. 2: The therapeutic product of claim 1, wherein the viralpathogen is an influenza virus, a hepatitis C virus, a hepatitis Bvirus, a respiratory syncytial virus, an adenovirus, or a rotavirus. 3:The therapeutic product of claim 1, wherein the serious adverse reactionis Guillain-Barre syndrome-like condition, death, abortion, immature ordelayed delivery, fetal death, or neonatal death. 4: The therapeuticproduct of claim 1, wherein the infection is an influenza infection andthe vaccination is influenza vaccination. 5: The therapeutic product ofclaim 1, wherein the product comprises about 0.001 g to about 100 g ofimmunoglobulin or about 0.1 mL to 1000 mL of serum or plasma. 6: Thetherapeutic product of claim 1, wherein the product comprises about 0.01mg to 500 mg of a specific antibody to a viral pathogen and about 0.001g to about 100 g of immunoglobulin, or about 0.1 mL to 1000 mL of serumor plasma. 7: The therapeutic product of claim 1, wherein the productcomprises about 0.1 mg/mL to about 20 mg/mL or about 0.1 mg/g to about20 mg/g of N-acetylneuraminic acid and about 0.001 g to about 100 g ofimmunoglobulin, or about 0.01 mg to 500 mg of a specific antibody to aviral pathogen, or about 0.1 mL to about 1000 mL of serum or plasma. 8:The therapeutic product of claim 1, wherein the product is a solution,lyophilized, an injectable, an infusion, or a form conjugated to anano-particle.